Bradley K. Wacker, Jennifer L. Perfater and Jeffrey M. Gidday Hypoxic preconditioning induces stroke tolerance in mice via a cascading HIF, sphingosine kinase, and CCL2 signaling pathway Journal of Neurochemistry 123
Signaling the preconditioning genomic response
Preconditioning for stroke tolerance with hypoxia, cobalt, and FTY720 requires HIF activity and SphK2-generated S1P signaling via the S1P1 receptor. In turn, cross-talk/feedback between HIF and S1P signaling up-regulates CCL2 expression to induce this epigenetic response. The identification herein of multiple upstream mediators of ischemic tolerance provides several targets of translational relevance for preconditioning in humans.
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